1. Field of the Technology
The disclosure generally relates to the field of magnetically guided catheters. Specifically, to a mapping and ablation catheter having an embedded MOSFET sensor array for detecting local electrophysiological parameters such as biopotential signals and tissue contact pressure within an arterial structure and more specifically in the renal artery plexus, and further for providing a means to remotely guide, control, and deliver the catheter fitted with a magnetic element. The apparatus with its sensor array and the means for guiding and controlling the movement of the device is described in connection with the current clinical method of neuro-modulation so as to normalize a patient's blood pressure.
2. Description of the Prior Art
Clinical Observation on Renal Denervation Procedure
It has long been known that the kidneys play an important role in the genesis and maintenance of hypertension (HTN). The seminal studies of Goldblatt in 1934 showed that reduction of blood flow to a kidney can cause severe hypertension, now known to be the result of activation of the renin-angiotensin-aldosterone system (RAS). The RAS peptide chain-reaction that results in HTN can be reversed by restoring blood flow to the affected kidney in this model of vascular disease of the kidneys.
The kidney's role in hypertension is not only restricted to instances of decreased blood flow. It is known that the kidney has a rich innervation by sympathetic efferent nerve terminals and by a rich network of afferent (sensory) nerve endings. The efferent nerve endings cause renal vascular constriction, stimulate renin release and also enhance sodium and water retention, all of which lead to HTN. The afferent nerve endings appear to signal the brain of changes in the chemical composition of blood and urine and mechanical changes in the renal pelvis. These signals appear to evoke sympathetic excitation, resulting in activation of the sympathetic efferent nerves and resultant HTN. Renal nerves have also been implicated in the progression of chronic kidney disease associated with chronic hypertension. Of great importance to the concept of renal artery denervation, the renal artery is the site of many of the afferent and efferent nerve endings.
Based on the above physiology, surgeons first began in the 1930s to attempt to disconnect the autonomic nervous system from the kidney by performing surgical sympathectomy in patients with hypertension. These surgical approaches were ultimately abandoned because they were associated with unacceptable peri-operative morbidity and mortality.
The old concept of treating refractory HTN with renal denervation has recently been resurrected in the form of catheter based RF energy ablation of renal nerve endings within the renal artery. Initial positive results have spawned larger trials designed to show that application of RF energy within the lumen of both renal arteries can reduce blood pressure in selected patients with drug-resistant HTN. In essence, the RF catheter is advanced into the renal arteries and 4-6 discrete low-power RF energy applications are applied along the length of both arteries. This is done on a purely anatomic basis, without acute physiologic or electric endpoints for energy application. For example, it is currently unknown whether the ablative energy destroys the afferent or efferent nerve endings, neither, or both. Long-term complications from random application of RF energy into the renal arteries, such as late renal artery stenosis, are an obvious concern that needs to be evaluated.
Hypertension, heart failure, and chronic kidney disease represent a significant and growing global health issue. Current therapeutic strategies for these conditions are mainly based on lifestyle interventions and pharmacological approaches, but the rates of control of blood pressure and the therapeutic efforts to prevent progression of heart failure, chronic kidney disease, and their sequelae remain unsatisfactory, and additional options are required.
The contribution of renal sympathetic nerve activity to the development and progression of these disease states has been convincingly demonstrated in both preclinical and human experiments. Preclinical experiments in models of hypertension, myocardial infarction, heart failure, chronic kidney disease, and diabetic nephropathy have successfully used renal denervation as both an experimental tool and a therapeutic strategy.
Surgical renal denervation has been shown to be an effective means of reducing sympathetic outflow to the kidneys, increasing urine output and reducing renin release, without adversely affecting other functions of the kidney. The human transplant experience has clearly demonstrated that the denervated kidney reliably supports electrolyte and volume homeostasis in free-living humans. On the basis of these findings and in view of the demand for alternative treatment options, targeting the renal sympathetic nerves as a major player in the pathophysiology of hypertension, kidney disease, and heart failure is a very attractive therapeutic approach.
Role of Renal Sympathetic Nerves in Cardiovascular and Kidney Disease
The renal sympathetic nervous system has been identified as a major contributor to the complex pathophysiology of hypertension, states of volume overload (such as heart failure), and progressive renal disease, both experimentally and in humans. (See DiBona GF, “The sympathetic nervous system and hypertension: recent developments,” Hypertension, 2004; 43:147-150). It is now widely accepted that essential hypertension is commonly neurogenic, both initiated and sustained by sympathetic nervous system over activity, (see, Esler M, Jennings G, Lambert G. Norepinephrine, “Release and the pathophysiology of primary human hypertension,” Am J. Hypertens. 1989; 2:140S-146S)
There is now compelling evidence to suggest that sensory afferent signals originating from the diseased kidneys are major contributors to initiate and sustain renal sympathetic efferent activation in this patient group, which facilitates the occurrence of the well-known adverse consequences of chronic sympathetic over activity, such as hypertension, (see, Schlaich M P, Lambert E, Kaye D M, Krozowski Z, Campbell D J, Lambert G, Hastings J, Aggarwal A, Esler M D, “Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and angiotensin neuromodulation,” Hypertension, 2004; 43:169-175).
The sympathetic nerves to the kidneys terminate in the blood vessels, the juxtaglomerular apparatus, and the renal tubules. Stimulation of the renal sympathetic nerves causes increased renin release, increased sodium reabsorption, and a reduction of renal blood flow, (see, Zanchetti AS, “Neural regulation of renin release: experimental evidence and clinical implications in arterial hypertension,” Circulation, 1977; 56:691-698).
Pharmacological strategies to thwart the consequences of renal efferent sympathetic stimulation include centrally acting sympatholytic drugs, Beta-blockers. However the current pharmacological strategies have significant limitations, including limited efficacy, compliance issues, adverse effects, and others. Thus, a compelling need for additional or alternative therapies exists. Renal denervation potentially offers a more direct, organ-specific strategy by targeting a mechanism crucially involved in initiating this vicious cycle. The kidneys communicate with integral structures in the central nervous system via the renal sensory afferent nerves, Renal sensory afferent nerve activity directly influences sympathetic outflow to the kidney.
Abrogation of renal sensory afferent nerves has been demonstrated in various models to have salutary effects not only on blood pressure but also on organ-specific damage caused by chronic sympathetic over activity, (see, DiBona GF, “Sympathetic nervous system and the kidney in hypertension,” Curr Opin Nephrol Hypertens. 2002; 11:197-200). Thus, renal denervation is likely to be valuable in the treatment of several clinical conditions characterized by increased overall and particularly renal sympathetic activity.
Therapeutic renal denervation in humans suffers from a treatment which enables the physician to perform the procedure in an optimal and safe mode, with consistent and repeatable outcome. The irregular success of the procedure (notably in the reduction of blood pressure) might appropriately be attributed to the occasional renal denervation that was effected by the surgical procedure. The occasional dramatic success of the unproven surgical strategy fuels enthusiasm for the development of a safe, effective, and targeted procedure to functionally denervate the human kidneys.
Surgical methods of sympathectomy were associated with high perioperative morbidity and mortality, as well as long-term complications, including bowel, bladder, and erectile dysfunction, in addition to profound postural hypotension, (see, Smithwick R H, Thompson J E, “Splanchnicectomy for essential hypertension; results in 1,266 cases,” JAMA. 1953; 152:1501-1504). The renal sympathetic nerves are derived from numerous spinal ganglia, and paraspinal ganglionectomy has been associated with severe and systemic adverse effects. The sympathetic renal nerves arborize throughout the adventitia of the renal artery, eliminating convenient anatomic access.
The retroperitoneal location of the kidney increases the technical difficulty of access to the nerves. In spite of these many obstacles, recent developments appear to have the potential to overcome these anatomic and technical difficulties and to provide new hope for the treatment of resistant hypertension and perhaps other clinical conditions commonly associated with increased renal sympathetic nerve activity.
In a recently published safety and proof-of-concept trial, a novel, percutaneous, catheter-based approach was applied to selectively ablate the renal sympathetic nerves without affecting other abdominal, pelvic, or lower extremity innervations, (see, Krum H, Schlaich M, Whitbourn R, Sobotka P A, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham WT, Esler M., “Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study,” Lancet. 2009; 373: 1275-1281).
In spite of these many obstacles, recent developments appear to have the potential to overcome these anatomic and technical difficulties and to provide new hope for the treatment of resistant hypertension.
In summary, catheter-based therapeutic renal denervation appears to be a quick and safe procedure that resulted in a large and persistent decrease in blood pressure in patients resistant to multiple existing antihypertensive drug classes. Taken together, the safety and efficacy findings of these initial studies confirm the importance of renal sympathetic nerves in resistant hypertension and suggest that renal sympathetic denervation has the potential of therapeutic benefit in this patient population, (see, Markus P. Schlaich, Paul A. Sobotka, Henry Krum, Robert Whitbourn, Anthony Walton and Murray D. Esler, “Renal Denervation as a Therapeutic Approach for Hypertension: Novel Implications for an Old Concept,”, Hypertension 2009, 54:1195-1201).
Discussion of Prior Art
The prior art discussion is centered on three fundamental aspects of the technology: The ability of the physician to navigate and control the translation and rotation of the catheter within the vasculature tree branching safely and accurately, the ability of the mapping system to identify specific location of the renal plexus active area by measuring the biopotential, and the ability of the guidance and control system to deliver the necessary amount of energy safely and accurately.
The literature provides us with evidence that due to the fact that renal sympathetic nerves are derived from numerous spinal ganglia, and paraspinal ganglionectomy has been associated with severe and systemic adverse effects. The sympathetic renal nerves arborize throughout the adventitia of the renal artery, eliminating convenient anatomic access. Surgical methods of sympathectomy were associated with high perioperative morbidity and mortality, as well as long-term complications, including bowel, bladder, and erectile dysfunction, in addition to profound postural hypotension, (see Smithwick R H, Thompson J E, “Splanchnicectomy for essential hypertension; results in 1,266 cases,” JAMA. 1953; 152: 1501-1504).
The retroperitoneal location of the kidney increases the technical difficulty of access to the nerves. In spite of these many obstacles, recent developments appear to have the potential to overcome these anatomic and technical difficulties and to provide new hope for the treatment of resistant hypertension and perhaps other clinical conditions commonly associated with increased renal sympathetic nerve activity.
To achieve such outcome the system must be able to drive the diagnostic and therapeutic tool or catheter through the arterial tree by providing the necessary translational as well as rotational forces so as to travel safely to the target, such as the renal artery plexus. This task is best described in by the prior art as a “magnetically guided catheter”.
Guidance and Control
There is a considerable library of prior patents wherein attempts have been made to control the movement of a catheter through the body lumens. The prior art of guiding and controlling a catheter for the specific diagnostic and therapeutic procedure involving renal denervation and generally the ability of a manual manipulation of catheter to perform neuromodulation, suffers from the fundamental inability of controlling a tethered device while being suspended in a lumen of the body cavity. The inherent instability of a tethered device is known to those familiar with the art of guiding and controlling a permanent magnet in three dimensional spaces with five degrees of freedom, a condition described formally as the Earnshaw exclusion principle.
The disclosed solutions so far provided by the prior art fail to address the fact that a medical device such as catheter with a specific mass necessitates a magnetic force and force gradient sufficient to rotate and translate such device in a suspended state. The prior art provides for literal descriptions of such alleged physical control, but do not disclose any solution that practically enables such control. This failure to enable a solution to the problem renders such prior art embodiments impractical and unusable.
Because of these drawbacks, what is needed is further development of the method and system such as described by the embodiments in Shachar, “Apparatus And Method For Catheter Guidance Control And Imaging”, U.S. Pat. No. 7,769,427, which discloses a magnetically guided catheter, a system describing a magnetic guidance control and imaging method, and an apparatus using a magnetic field and field gradient to rotate, translate and levitate a medical device within a body cavity while navigating such tool or catheter through the arterial tree.
Recently, magnetic systems have been disclosed wherein magnetic fields produced by one or more electromagnets are used to guide and advance a magnetically-tipped device. The electromagnets in such systems produce large magnetic fields that are potentially dangerous to medical personnel and that can be disruptive to other equipment. A novel solution to the limitations noted by the art was developed by the introduction of a magnetic guidance system titled “Catheter Guidance Control and Imaging apparatus (CGCI)”, by Magnetecs corp. of Inglewood Calif. The properties and embodiments of the “CGCI” apparatus and methods are detailed by the following patents and patent application publications: U.S. Pat. No. 7,769,427, Apparatus and Method for Catheter Guidance Control and Imaging; 2006/0116634, System and Method for Controlling Movement of a Surgical Tool; 2006/0114088, Apparatus and Method for Generating a Magnetic Field; 2006/0116633, System and Method for a Magnetic Catheter Tip; U.S. Pat. No. 7,280,863, System and Method for Radar-Assisted Catheter Guidance and Control; 2008/0027313, System and Method for Radar-Assisted Catheter Guidance and Control; 2007/0016006, Apparatus and Method for Shaped Magnetic Field Control for Catheter, Guidance, Control, and Imaging; 2007/0197891, Apparatus for Magnetically Deployable Catheter with Mosfet Sensor and Method for Mapping and Ablation; 2009/0248014, Apparatus for Magnetically Deployable Catheter with Mosfet Sensor and Method for Mapping and Ablation; 2008/0249395, Method And Apparatus for Controlling Catheter Positioning and Orientation; Ser. No. 12/103,518, Magnetic Linear Actuator for Deployable Catheter Tools; 2009/0253985, Apparatus and Method for Lorentz-Active Sheath Display and Control of Surgical Tools; 2009/0275828, Method and Apparatus for Creating a High Resolution Map of the Electrical and Mechanical Properties of the Heart; 2010/0130854, System and Method for a Catheter Impedance Seeking Device; Ser. No. 12/475,370, Method and Apparatus for Magnetic Waveguide Forming a Shaped Field Employing a Magnetic Aperture for Guiding and Controlling a Medical Device; Ser. No. 12/582,588, Method for Acquiring High Density Mapping Data With a Catheter Guidance System; Ser. No. 12/582,621, Method for Simulating a Catheter Guidance System for Control, Development and Training Applications; Ser. No. 12/615,176, Method for Targeting Catheter Electrodes; Ser. No. 12/707,085, System and Method for Using Tissue Contact Information in the Automated Mapping of Coronary Chambers Employing Magnetically Shaped Fields; PCT/US2009/064439, System and Method for a Catheter Impedance Seeking Device; PCT/US2010/036149, Method and Apparatus for Magnetic Waveguide Forming a Shaped Field Employing a Magnetic Aperture for Guiding and Controlling a Medical Device; PCT/US2010/052696, Method for Acquiring High Density Mapping Data With a Catheter Guidance System; and PCT/US2010/052684, Method for Simulating a Catheter Guidance System for Control, Development and Training Applications. Each of the above listed patents and patent application publications are incorporated in their entirety by reference herein.
Prior Art and Current Renal Denervation Procedures
The prior art and its various embodiments as annotated by the patents and patent application publications noted below and are centered on the ability of the devices and systems to achieve the clinical outcome of affecting neuromodulation by means defined by the embodiments of this application.
Beetel, Robert J. et al., U.S. Pat. Application No. 2011/0200171, “Methods and apparatus for renal neuromodulation via stereotactic radiotherapy,” describes methods and apparatus for renal neuromodulation via stereotactic radiotherapy for the treatment of hypertension, heart failure, chronic kidney disease, diabetes, insulin resistance, metabolic disorder or other ailments. Renal neuromodulation may be achieved by locating renal nerves and then utilizing stereotactic radiotherapy to expose the renal nerves to a radiation dose sufficient to reduce neural activity. A neural location element may be provided for locating target renal nerves, and a stereotactic radiotherapy system may be provided for exposing the located renal nerves to a radiation dose sufficient to reduce the neural activity, with reduced or minimized radiation exposure in adjacent tissue. Renal nerves may be located and targeted at the level of the ganglion and/or at postganglionic positions, as well as at pre-ganglionic positions.
Deem, Mark et al., U.S. Pat. No. 7,653,438, “Methods and apparatus for renal neuromodulation,” describes methods and apparatus for renal neuromodulation using a pulsed electric field to effectuate electroporation or electrofusion. It is expected that renal neuromodulation (e.g., denervation) may, among other things, reduce expansion of an acute myocardial infarction, reduce or prevent the onset of morphological changes that are affiliated with congestive heart failure, and/or be efficacious in the treatment of end stage renal disease. Embodiments of the present invention are configured for percutaneous intravascular delivery of pulsed electric fields to achieve such neuromodulation.
Demarais, Denise et al., U.S. Pat. Application No. 2006/0206150, “Methods and apparatus for treating acute myocardial infarction,” describes methods and apparatus for treating acute myocardial infarction, e.g., via a pulsed electric field, via a stimulation electric field, via localized drug delivery, via high frequency ultrasound, via thermal techniques, etc. Such neuromodulation may effectuate irreversible electroporation or electrofusion, necrosis and/or inducement of apoptosis, alteration of gene expression, action potential attenuation or blockade, changes in cytokine up-regulation and other conditions in target neural fibers. In some embodiments, neuromodulation is applied to neural fibers that contribute to renal function. In some embodiments, such neuromodulation is performed in a bilateral fashion. Bilateral renal neuromodulation may provide enhanced therapeutic effect in some patients as compared to renal neuromodulation performed unilaterally, i.e., as compared to renal neuromodulation performed on neural tissue innervating a single kidney.
Gelfand, Mark et al., U.S. Pat. Application No. 2008/0213331, “Methods and devices for renal nerve blocking,” describes a method and apparatus for treatment of cardiac and renal diseases associated with the elevated sympathetic renal nerve activity by implanting a device to block the renal nerve signals to and from the kidney. The device can be a drug pump or a drug eluding implant for targeted delivery of a nerve-blocking agent to the periarterial space of the renal artery.
Demarais, Denise et al., U.S. Pat. Application No 2010/0191112, “Ultrasound apparatuses for thermally-induced renal neuromodulation,” describes methods and apparatus for thermally-induced renal neuromodulation. Thermally-induced renal neuromodulation may be achieved via direct and/or via indirect application of thermal energy to heat or cool neural fibers that contribute to renal function, or of vascular structures that feed or perfuse the neural fibers. In some embodiments, parameters of the neural fibers, of non-target tissue, or of the thermal energy delivery element, may be monitored via one or more sensors for controlling the thermally-induced neuromodulation. In some embodiments, protective elements may be provided to reduce a degree of thermal damage induced in the non-target tissues.
Wu, Andrew et al., U.S. Pat. Application No. 2011/0264011, “Multi-directional deflectable catheter apparatuses, systems, and methods for renal neuromodulation,” describes multi-directional deflectable catheter apparatuses, systems, and methods for achieving renal neuromodulation by intravascular access. One aspect of the present application, for example, is directed to apparatuses, systems, and methods that incorporate a catheter treatment device comprising an elongated shaft. The elongated shaft is sized and configured to deliver a thermal element to a renal artery via an intravascular path. Thermally or electrical renal neuromodulation may be achieved via direct and/or via indirect application of thermal and/or electrical energy to heat or cool, or otherwise electrically modulate, neural fibers that contribute to renal function, or of vascular structures that feed or perfuse the neural fibers.
Demarais, Denise et al., U.S. Pat. No. 7,617,005, “Methods and apparatus for thermally-induced renal neuromodulation,” describes methods and apparatus for thermally-induced renal neuromodulation. Thermally-induced renal neuromodulation may be achieved via direct and/or via indirect application of thermal energy to heat or cool neural fibers that contribute to renal function, or of vascular structures that feed or perfuse the neural fibers. In some embodiments, parameters of the neural fibers, of non-target tissue, or of the thermal energy delivery element, may be monitored via one or more sensors for controlling the thermally-induced neuromodulation. In some embodiments, protective elements may be provided to reduce a degree of thermal damage induced in the non-target tissues.
Zarins, Denise et al., U.S. Pat. Application No. 2008/0255642, “Methods and systems for thermally-induced renal neuromodulation,” describes methods and system for thermally-induced renal neuromodulation. Thermally-induced renal neuromodulation may be achieved via direct and/or via indirect application of thermal energy to heat or cool neural fibers that contribute to renal function, or of vascular structures that feed or perfuse the neural fibers. In some embodiments, parameters of the neural fibers, of non-target tissue, or of the thermal energy delivery element, may be monitored via one or more sensors for controlling the thermally-induced neuromodulation. In some embodiments, protective elements may be provided to reduce a degree of thermal damage induced in the non-target tissues. In some embodiments, thermally-induced renal neuromodulation is achieved via delivery of a pulsed thermal therapy.
Leung, Mark S. et al., U.S. Pat. Application No. 2011/0264075, “Catheter apparatuses, systems, and methods for renal neuromodulation,” describes catheter apparatuses, systems, and methods for achieving renal neuromodulation by intravascular access. One aspect of the present application, for example, is directed to apparatuses, systems, and methods that incorporate a catheter treatment device comprising an elongated shaft. The elongated shaft is sized and configured to deliver an energy delivery element to a renal artery via an intravascular path. Thermal or electrical renal neuromodulation may be achieved via direct and/or via indirect application of thermal and/or electrical energy to heat or cool, or otherwise electrically modulate, neural fibers that contribute to renal function, or of vascular structures that feed or perfuse the neural fibers.
Bin Yin et al US 2011/0137200, describes a system and a method in which an electrophysiological signal is sensed capacitively with at least two closely spaced electrodes such that the electrodes experience strongly correlated skin-electrode distance variations. To be able to derive a motion artifact signal, the capacitive coupling between the electrodes and skin is made intentionally different. With a signal processing means the motion artifact signal can be removed from the measured signal to leave only the desired electrophysiological signal. Since the measured quantity is dependent on the electrode-skin distance itself, the system and method do not need to rely on the constancy of a transfer function. Hereby, they give reliable motion artifact free output signals.
Chii-Wann Lin et al in US 2010/0145179, describes a micro electrode of a high-density micro electrode array is connected to the same conducting wire. Serial switches enable sequential electrical connection of the micro electrode array. Given reasonable temporal resolution, the separation interval of two consecutive instances of the same micro electrode entering the ON state matches the temporal resolution. The micro electrode array has simple layout and small area, thereby maximizing the number of micro electrodes installed per unit area.
Paul Haefner in US 2007/0293896 describes an arrhythmia discrimination device and method involves receiving electrocardiogram signals and non-electrophysiological signals at subcutaneous locations. Both the electrocardiogram signals and non-electro physiologic signals are used to discriminate between normal sinus rhythm and an arrhythmia. An arrhythmia may be detected using electrocardiogram signals, and verified using the non-electro physiologic signals. A detection window may be initiated in response to receiving the electrocardiogram signal, and used to determine whether the non-electro physiologic signal is received at a time falling within the detection window. Heart rates may be computed based on both the electrocardiogram signals and non-electro physiologic signals. The rates may be used to discriminate between normal sinus rhythm and an arrhythmia, and used to determine absence of an arrhythmia.
Additional applications supporting the existing art are listed herein for reference; U.S. patent And application Nos.: U.S. Pat. Nos. 7,620,451; 7,937,143; 2006/0212078; 2006/0276852; 2009/0036948; 2010/0168739; 2010/0222854; 2011/0200171; U.S. Pat. No. 7,647,115; 2006/0142801; 2006/0265014; 2007/0129720; 2007/0265687; 2009/0076409; 2010/0174282; 2010/0249773; 2011/0257564; U.S. Pat. Nos. 7,620,451; 7,937,143; 2006/0212078; 2006/0276852; 2009/0036948; 2010/0168739; 2010/0222854; 2011/0200171; U.S. Pat. No. 7,647,115; 2006/0142801; 2006/0265014; 2007/0129720; 2007/0265687; 2009/0076409; 2010/0174282; 2010/0249773; and 2011/0257564.
The methods and the examples noted by the applications and patents listed above, further describe and elaborate on the existing art of renal denervation using electrodes technology, optical, ultrasonic and variety of techniques employing inferred radiation and x-ray. All the above methods are used in order to sense or identify the location of the nerve bundle, such as the right or left plexus located within the renal artery. All the patents and applications elaborate on the ability of the operator (physician), to manipulate the catheter by translating and rotating distal end to its intended target, e.g. the renal artery and specifically to the area where the right or left plexus is located. The patents with its collected embodiments and their associated specification clearly inform us of the inherent difficulties in navigating the catheter distal end from its origin (the vascular tree) to its relevant anatomical and significant clinical site. These challenges of navigating the catheter by manual manipulation with the aid of electro-mechanical mechanisms are the mainstay of the current applications. The ability of the operator to perform diagnostic-(identifying the location of the renal plexus), while travelling through the vascular tree, and subsequently performing a therapeutic procedure of denervation the renal artery, these functionalities of driving the catheter to its intended anatomical site and delivering energy to perform the procedure is the main challenge that this application with its novel detection and its remote navigation is solving as it is defined by the specification and embodiments of this application.
As shown above, the prior art suffers from the same limitations noted above as these techniques, methods, and examples uses the manual manipulations to drive the catheter distal end, while employing a variety of technologies to perform the clinical procedure of renal denervation. We supplement the review of the prior art, in order to clarify and emphasize the inherent limitations of the current techniques methods and examples so as to highlight the categorical difference of the prior art and the current invention. At the center of our differentiation is the ability to drive the catheter by manual technique using mechanical mechanism of influencing the distal end of the catheter so as to overcome the complex anatomy of the vascular tree in order to rotate and translate the catheter to its desired anatomical site, and once arrived to the site, the operator must identify precisely the renal plexus so as to deliver the energy for the purpose of denerving the active control of the sympathetic nerve system from influencing the metabolic control of that system.
It is therefore clear, that current art of manipulating the distal end of the catheter is limited to the mechanical degrees of freedom afforded by the use of varieties of manipulating the catheter distal end by the ability of such tools and techniques to influence the position and orientation of the catheter by means that are sub-optimal and that such methods and apparatus are subject to the limitations noted and that such limitations are directly related to the successful outcome of the clinical results. The limitations of guiding the catheter trough the vascular tree are known for those familiar with the art. The solution proposed by the invention will be clear and the advantage of using magnetically fitted catheter with its novel apparatus and system with MOSFET sensing array will improve the safety and efficacy of the current art.
As shown by the prior art review section, the mainstay of the art is the ability of the operator to manipulate the catheter relaying on manual translation and rotation of the distal end so as to acquire the optimal position of the catheter and by sensing the biopotential and relaying on the operator dexterity to place the catheter firmly in its desired location so as to be able to deliver curative energy in performing the procedure termed in the art as “renal denervation”.
MOSFET Sensor Array
The prior art is primarily centered on the novelty of employing a MOSFET sensor array for the detection and recording of bioelectric potential as the use of the MOSFET sensor array embedded within a magnetically guided catheter is highlighted and a detailed description of the use of such method and its proposed apparatus in clinical procedure is described. Generally this procedure is a twofold operation it involve first the mapping of the site so as to diagnose and define the relevant optimal location of the ablation of nerve or ganglionic plexus. The functional modification is described so as to affect the performance of such bioelectrical activity. The remodeling of neural activity or neuromodulation is best achieved by the improvements proposed by this invention.
It is clear to those familiar with the art of electrophysiology mapping, that methods using electrode technologies of all different combinations as noted by the prior art, suffer from the inability to differentiate between signals emanating from near and far fields as the electrodes in the prior art are typically made of metal-electrolyte interface. The interface impedance in this relation is represented as a capacitor, and in a non-polarized electrode, the impedance is represented as a resistor. But in practice both capacitive and resistive components are present in the existing art, while the new method and the accompanying apparatus to this invention employ the MOSFET isolated junction, which measure the action potentials without the parasitic capacitive or resistive loads noted by the prior art.
The discussion relating to the prior art is set as a background in order to contrast and highlight the preferred embodiments of this application. The ability to perform a surgical intervention by minimally invasive use of catheter requires a precise and stable navigation and control of the distal end of the catheter. The use of magnetically guided tool as described by the CGCI coupled with the ability of the sensory apparatus to define accurately the site of the bioelectric potential and further the ability of the system to achieve the target by accurately arriving to the site is the main stay of the proposed application. The clear advantage of magnetic guidance and control of the catheter with its MOSFET sensor array is demonstrable and improve the art of neuromodulation as it provide for precision and safety of such operation.
The ability of MOSFET sensor array to identify the location of bioelectrical signal with fidelity that eliminate the current electrode technology with its short comings associated with “far field/near fields” averaging distortion and specifically the sensor's ability to depict a small bioelectric potential in the orders of micro-volts.
In spite of these many obstacles, recent developments in magnetic navigation on the one hand and signal detection employing a MOSFET sensor array appear to have the potential to overcome these anatomic and technical difficulties and further improve the indices of success by reducing unnecessary injury by the use of local monitoring of nerve impulse activity. We refer to the literature and the experimental work conducted by the C. Williams study, as in the example it is clear that it needs to define a local bioelectrical measurements, (not compromised by the averages associated with different dielectric and conductivity measures) is essential in preserving the fidelity and integrity of the signal measured, that the underlying mechanism of impedance variations within nervous tissue, (wherein the presence of myelinated tracts giving a relatively low conductivity), results in conductivity change of the tissue rises as the ion-containing, extra cellular fluid which provides for more conduction paths. The study further reported that typical values for white matter are 700 ohm-cm; for grey matter, 300 ohm-cm; and the skull is typically 5000 ohm-cm. This variation of conductivity in different tissues is the main reason why the bioelectric potentials need to be measured locally, so as to avoid the SNR (Signal to Noise Ratio) distortion associated with for example in measuring global EEG indications. In addition to differences in local conductivity between gray and white matter, the measurements from global EEG measurements are further compromised secondary to the use of medications administered at the time of surgery such as anesthetic agents, dexamethasone (given to reduce brain swelling), mannitol (an osmotic agent used for diuresis), and lasix (osmotic agent used for diuresis). Other drugs such as intraoperative anticonvulsants (i.e. phenytoin or keppra) may cause distortions in local neurophysiology. The net result, cell swelling, is really a combination of pressure across arterial cross section, medications administered, and anesthesia. Cellular swelling affects both neurons, of which neurophysiological changes are best, appreciated on a local intraoperative biopotential rather the prior art methods of electrodes detection with ground path with few feet away from the measurement site coupled with averaging of near and far fields due to the inability of the current electrodes technology to discern such small signal as shall be clear when reviewing the novelty proposed by the invention. Therefore, these cellular changes due to metabolic assimilation of mechanical as well as chemical changes are mirrored by electrical manifestations, resulting in a state which the current invention is solving.